Lipid-lowering effects of oleanolic acid in hyperlipidemic patients
Lipid-lowering effects of oleanolic acid in hyperlipidemic patients
复制标题
齐墩果酸对高脂血症患者的降脂作用
DOI：
10.1016/s1875-5364(18)30065-7
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发表时间：
2018-05-01
影响因子：
4.6
通讯作者：
Liu Jun
中科院分区：
文献类型：
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作者：
Luo Han-Qiong;Shen Jie;Liu Jun
油酸（oleanecidic acid，OA）是从中药油橄榄（oleaeuropaeal）中提取的一种五环三萜类化合物，自20世纪70年代以来，OA作为一种保肝药物在我国临床上得到应用。在我们以前的研究中，我们观察到OA可以改善动物模型的高脂血症。在本研究中，我们进行了一项小规模的临床试验，以评估OA在高血脂症患者中的降脂作用。高脂血症患者口服OA 4片，每日3次，每次4片，共4周。分别于治疗前后采集患者的血液样本。测量生物学参数。并对3例患者的血液样本进行了基因芯片检测。OA给药后，血清TC、TG和HDL C水平显著降低。DNA微阵列分析结果显示，OA治疗后，21个mRNA的表达发生了显著变化。生物信息学分析显示，OA处理后17个mRNA表达上调，4个mRNA表达下调。选择5种mRNA（CACNA 1B、FCN、STEAP 3、AMPH和NR 6A 1），通过qRT-PCR验证表达水平。因此，OA管理差异调节参与脂质代谢的基因的表达。这些数据为OA改善高脂血症提供了临床证据，也为OA治疗高脂血症的分子机制提供了新的见解。
Oleanolic acid (OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks (4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 mRNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 mRNAs were up-regulated and 4 mRNAs were down-regulated significantly after OA treatment. Five mRNAs (CACNA1B, FCN, STEAP3, AMPH, and NR6A1) were selected to validate the expression levels by qRT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.